MXPA01000264A - Method for preparing hydroxymethylthiobutyric acid - Google Patents

Abstract

The invention concerns a novel method for preparing hydroxymethylthiobutyric acid by sulphuric hydrolysis of hydroxymethylthiobutyronitrile.

Description

PROCEDURE FOR THE PREPARATION OF HYDROXIMETILTIOBUTYRIC ACID DESCRIPTION OF THE INVENTION The present invention relates to a new process for the preparation of 2-hydroxy-4-methylthiobutyric acid. It relates more particularly to a hydrolysis process of 2-hydroxy-4-methylthiobutyronitrile. 2-Hydroxy-4-methylthiobutyric acid (AHMTB) is known and is used as an analogue of methionine to nourish livestock and mainly poultry. This product is marketed under the trademarks Rhodimet AT 88 ™ or Alimet ™. It is known how to prepare 2-hydroxy-4-methylthiobutyric acid by different hydrolysis processes of 2-hydroxy-4-methylthiobutyroniyl (HMTBN). The hydrolysis is carried out with a mineral acid such as hydrochloric or sulfuric acid, or it can even be carried out by enzymatic hydrolysis. British Patent GB No. 915 193, teaches the hydrolysis of 2-hydroxy-4-methylthiobutyronitrile in 2-hydroxy-4-methylthiobutyric acid, in the presence of a mineral acid. This patent describes the continuous hydrolysis of 2-hydroxy-4-methylthiobutyronitrile with Itef sulfuric acid: 125936 diluted and the obtained organic acid is recovered by extraction with an ether. As the hydrolysis is carried out continuously in a stirred reactor, the process described in this patent effects an incomplete hydrolysis of the initial nitrile and, consequently, there is the presence of undesirable derivatives that can not be given to the animals without risk. It is also known, from US Pat. No. 4,524,077, to hydrolyse the same initial nitrile as 2-hydroxy-4-methylthiobutyronitrile, with two-step sulfuric acid, followed by an extraction of the hydrolysis medium with a non-miscible solvent with Water. The two-stage process consists of a first step using a sulfuric acid having a concentration between 50 and 70% by weight and at a temperature between 25 and 65 ° C. The introduction of 2-hydroxy-4-ethylthiobutyronitrile is carried out for 30 to 60 minutes and the hydrolysis of the nitrile in the corresponding amide is carried out for a period of 30 to 90 minutes. The 2-hydroxy-4-methylthiobutyramide is subsequently converted to 2-hydroxy-4-methylthiobutyric acid in a subsequent step of hydrolysis at a temperature ranging from 70 to 120 ° C. The final step of hydrolysis is carried out with an acid having a concentration comprised between 30 and 50% by weight. In practice, this concentration is obtained by the addition of water. Under these conditions, 2-hydroxy-4-methylthiobutyramide is converted to 2-hydroxy-4-methylthiobutyric acid in 60 to 180 minutes. To transform the nitrile into acid, the molar ratio of sulfuric acid to nitrile is between 1 and 1.1. US Patent No. US 4,912,257 describes a process wherein the same nitrile, ie 2-hydroxy-4-methylthiobutyronitrile, is hydrolysed with sulfuric acid in such a way that the molar ratio of sulfuric acid to 2-hydroxy-4- methylthiobutyronitrile is between 0.5 and 2, to form a reaction mixture containing 20 to 50% by weight of sulfuric acid. The mixture is maintained at a maximum temperature of 50 ° C in a stirred reactor for 30 to 60 minutes. The second reaction step is carried out in a second reactor, which is heated to a temperature comprised between 60 and 140 ° C for about 5 to 6 hours. The Patent Application published with the No. WO 96/40630, describes the same hydrolysis reaction in two stages. The preferred ratio between sulfuric acid and 2-hydroxy-4-methylthiobutyronitrile is comprised, at the start of the reaction, between 1.15 and 1.25 and then, when the reaction is in a stationary stage, between 0.9 and 1.2 and preferably between 0.95. and 1.05. A number of examples were made to vary said relationship. All examples where the ratio is less than 0.88 show a transformation rate of 2-hydroxy-4-methylthiobutyronitrile less than 95%, which is very insufficient for an industrial exploitation. In this patent application, the conclusion is that a ratio of sulfuric acid to nitrile should be used, between 1.0 and 1.2. The disadvantage of using these amounts of sulfuric acid, comprised between 1.0 and 1.2 moles per mole of 2-hydroxy-4-methylthiobutyronitrile, is the fact that at the end of the reaction quantities of ammonium sulfate proportional to the amounts of acid are recovered. Sulfuric These high amounts of sulphate cause a large problem of industrial waste that is increasingly difficult to solve. In addition, the medium is strongly acidic and is very corrosive to heating and requires the use of exotic materials. From a reaction point of view, a ratio of 0.5 would seem sufficient, but chemically it is shown that these conditions are inoperative. It seems impossible to lower this molar ratio of sulfuric acid to nitrile below 0.88, which is the extreme limit that seems to be operable in the aforementioned patent application. Surprisingly, it seems that it is possible to perform the hydrolysis of 2-hydroxy-4-methylthiobutyronitrile in 2-hydroxy-4-methylthiobutyric acid with excellent yields, with a molar ratio of sulfuric acid to 2-hydroxy-4-methylthiobutyronitrile. between 0.6 and 0.88. It is preferred to use a molar ratio between 0.7 and 0.85. Preferably, the first step, which is a hydration reaction of 2-hydroxy-4-methylthiobutyronitrile in 2-hydroxy-4-methylthiobutyramide, is carried out in a highly concentrated sulfuric acid medium and in the presence of a sufficient amount of water to carry out this reaction. The speed of this reaction is inversely proportional to the amount of water. Thus, an amount of water at least equal to one mole of water per mole of 2-hydroxy-4-methylthiobutyronitrile is necessary and a molar amount of water comprised between 1 and 3.0 is preferred. Preferably a molar ratio between water and 2-hydroxy-4-methylthiobutyronitrile comprised between 1 and 2.5 is used. This low concentration of water greatly limits during the first stage the successive hydrolysis of 2-hydroxy-4-methylthiobutyramide into 2-hydroxy-4-methylthiobutyric acid. Thus, it is preferred during this first step that no more than 5%, preferably less than 2% by weight, of 2-hydroxy-4-methylthiobutyric acid be produced. Likewise, during this first step it is preferred to obtain a concentration of 2-hydroxy-4-methylthiobutyramide greater than 95% by weight and preferably greater than 98% by weight. The operating conditions used during this first stage are selected within limits that do not lead to the production of 2-hydroxy-4-methylthiobutyric acid, thus, it is preferred to work at a temperature below 60 ° C and preferably between 0 and 50 ° C. The reaction is preferably carried out in a continuous and serial reactor system, with a residence time of between 15 minutes and 2 hours. The reaction pressure of preference is selected between 0.01 and 3 bar. The second step of the reaction is a hydrolysis of 2-hydroxy-4-methylthiobutyramide in 2-hydroxy-4-methylthiobutyric acid, this is carried out in the presence of the remaining amount of sulfuric acid not consumed in the first stage and in the presence of a quantity of supplementary water that prevents phase separation in the reaction medium. This preferred stage is carried out in the presence of at least 28% by weight of water. As far as the reaction conditions are concerned, it is preferred to work at a temperature between 90 and 130 ° C. Preferably, operation is carried out at a pressure comprised between 0.5 and 5 bar. A pressure below atmospheric pressure makes it possible to eliminate traces of light gases which cause a bad odor, for example of the dimethyl sulfide, dimethyl disulfide and methyl mercaptan type. The slight excess of acid and the presence of ammonium acid sulfate greatly limit the corrosive power of the reaction medium at this temperature. According to a first embodiment according to the present invention, a concentrated 2-hydroxy-4-methylthiobutyronitrile solution is introduced into the first stage or an aqueous solution of 2-hydroxy-4-methylthiobutyronitrile is evaporated. When the procedure described above is carried out, that is to say when the water contained in an aqueous solution of 2-hydroxy-4-methylthiobutyronitrile is evaporated, the water evaporated in the first stage is advantageously recycled to the second stage. According to a better industrial embodiment of the present invention, the chaining of the steps is carried out starting from a solution of concentrated or dilute 2-hydroxy-4-methylthiobutyronitrile: According to a first industrial process, a solution of 2- is used. Concentrated hydroxy-4-methylthiobutyronitrile and concentrated H2SO4, containing less than 20% by weight of water. The concentrated 2-hydroxy-4-methylthiobutyronitrile at about 80% by weight and the concentrated sulfuric acid at about 90% by weight are fed to an apparatus wherein the 2-hydroxy-4-methylthiobutyronitrile is hydrated. In this way a solution containing 2-hydroxy-4-methylthiobutyramide is obtained. Water is added to this solution to prevent precipitation of the ammonium acid sulfate during the hydrolysis of 2-hydroxy-4-methylthiobutyramide. The solution obtained after the hydrolysis contains 2-hydroxy-4-methylthiobutyric acid. 2-Hydroxy-4-methylthiobutyric acid is recovered from this solution. For example, this method can be carried out continuously, semicontinuously or discontinuously. When the process is carried out continuously, the apparatuses used for the hydration of 2-hydroxy-4-methylthiobutyronitrile can comprise a first reactor with stirring with an external recirculation loop, which mainly serves to eliminate the calories released by the reaction. The hydration of the 2-hydroxy-4-methylthiobutyronitrile can be terminated in one or a plurality of reactors, stirred with a piston, preferably in series with the first reactor. In this way a solution containing 2-hydroxy-4-methylthiobutyramide is obtained. Water is added to this solution to prevent the precipitation of the ammonium acid sulfate during the hydrolysis of 2-hydroxy-4-methylthiobutyramide. The apparatuses used for the hydrolysis of 2-hydroxy-4-methylthiobutyramide can mainly comprise a first reactor with stirring. The hydrolysis of 2-hydroxy-4-methylthiobutyramide can be completed, in accordance with an industrial practice scheme, in one or a plurality of reactors, with piston stirring, connected in series with the first hydrolysis reactor. According to a second process starting from the dilute 2-hydroxy-4-methylthiobutyronitrile (for example 50%) and H2SO4, the following steps are carried out: Concentrated 2-hydroxy-4-methylthiobutyronitrile at approximately 50% by weight weight and sulfuric acid, are fed into an apparatus in which a part of the water contained in the reactants is removed to reach the conditions described in the first process and the 2-hydroxy-4-methylthiobutyronitrile is hydrated. In this way a solution containing 2-hydroxy-4-methylthiobutyramide is obtained. To this solution is added water, mainly the water removed before hydrolyzing the 2-hydroxy-4-methylthiobutyramide. The solution obtained after the hydrolysis contains 2-hydroxy-4-methylthiobutyric acid. 2-Hydroxy-4-methylthiobutyric acid is recovered from this solution. This method can be carried out, for example, continuously, semicontinuously or discontinuously. When the process is carried out continuously, the apparatus used for the hydration of 2-hydroxy-4-methylthiobutyronitrile may comprise a first stirred reactor operating at low pressure. The calories released by the reaction serve to vaporize the surplus water with respect to the conditions of the first method of the invention, from a concentrated solution of 2-hydroxy-4-methylthiobutyronitrile. The procedure may be completed in the manner indicated above. In accordance with a third practice method of the invention, it is carried out at the end of the second stage under pressure. The hydrolysis of 2-hydroxy-4-methylthiobutyramide is accelerated when the temperature increases. In order to exceed the boiling temperature of the reaction mixture, this step can be carried out under pressure. The mixture obtained subsequently is treated in the manner described in US Pat. Nos. 4,524,077 or US 4,912,257. Thus, US Pat. No. 4,912,257 describes, following the hydrolysis step, a neutralization step followed by a biphasic separation and drying step of each of the two phases, followed by, in one of the phases, a step of filtration and for the other phase a stage of crystallization. The final titration is done by adding water. US Pat. No. 4,524,077 consists in carrying out a direct extraction of the hydrolysis medium with a solvent not miscible with water, followed by an evaporation of the solvent in the presence of a quantity of water, in order to reduce the appearance of a dark color in the product obtained. The solvent is selected primarily from the group consisting of methylethyl ketone, methyl isobutyl ketone, methyltert-thiobutyl ether, diisopropyl ether and diethyl carbonate. The procedure described in US Pat. No. 4,912,257 consists in carrying out a two-phase separation. A neutralizing agent of the ammonia type is added to the medium leaving the hydrolysis step. The reaction mixture is separated into an organic phase (1) containing the desired acid and substituent salts. The aqueous phase (2) constitutes the other phase which essentially contains mineral salts, especially ammonium sulfate and traces of organic acid. The two phases can be evaporated to remove the water to obtain an organic solution of 2-hydroxy-4-methylthiobutyric acid that contains low amounts of ammonium sulfate that crystallizes, the latter is separated by filtration and the 2-hydroxy-4- acid methylthiobutyric is adapted to the desired commercial title (88% by weight) by the addition of water. Another solution consists in removing the mineral salts present in the solution of 2-hydroxy-4-methylthiobutyric acid by adding an organic solvent that is not very miscible with water, such as methylethyl ketone, methyl isobutyl ketone and diethyl carbonate. The insolubilization of an aqueous salt phase is then observed, the organic phase is solvent depleted by evaporation and the final solution of 2-hydroxy-4-methylthiobutyric acid is added to the commercial title by adding water. The aqueous phase (2) is evaporated to precipitate the mineral salts, essentially ammonium sulfate, which can be marketed as such, but which contains traces of malodorous organic derivatives. This aqueous phase can also be treated to deplete 2-hydroxy-4-methylthiobutyric acid. This depletion is carried out by the addition of a water-miscible solvent which is selected from the group consisting of methylethyl ketone, methyl isobutyl ketone and diethyl carbonate. The aqueous phase devoid of the organic derivatives is dried to isolate the odorless mineral salts and is marketed directly. The organic phase that was depleted is recycled, for example, with the phase of 2-hydroxy-4-methylthiobutyric acid in order to recover the quantities of acid extracted from the aqueous saline phase. The present invention will be described more fully with the help of the following examples, which should not be considered as limiting the invention. COMPARATIVE EXAMPLE 1 Test in a closed reactor in relation to H2S? 4 cyanohydrin = 1.2 In a 250 ml glass reactor equipped with: a double envelope whose temperature is regulated by circulation of an oil, a stirrer, a condenser, a thermocouple, a portion of 89 g of cyanhydrin at 78% by weight in water and 45 g of water is charged. In this way, 52% by weight cyanohydrin in water is obtained. Progressively add 65.5 g of 95% sulfuric acid (the molar ratio of sulfuric acid / cyanohydrin is equal to 1.2, the molar ratio of water / cyanohydrin is equal to 7.11) keeping the temperature of the reaction mixture below 60 ° C. The analysis of the medium shows that only 55% of the cyanohydrin is transformed. The selectivities of HMTBM and AHMTB are, respectively, 91 and 9%. The mixture is boiled at 112 ° C to complete the reactions. After 90 minutes under these conditions, the analysis of the medium shows that: - all the cyanohydrin has been transformed, the selectivities of HMTBM and AHMTB are, respectively, 0.4 and 99.6%. The weight ratio of the ammonium sulfate produced with respect to the AHMTB is 1.05. COMPARATIVE EXAMPLE 2 Comparative test in closed reactor, at a ratio of H2S? 4 / cyanohydrin = 0.81 In a glass reactor equipped with: a double envelope whose temperature is regulated by circulation of an oil, a stirrer, a condenser, a thermocouple, a portion of 60 g of cyanhydrin at 78% by weight in water and 60 g of water is charged.

Progressively add 30 g of 95% sulfuric acid (the molar ratio of sulfuric acid / cyanohydrin is equal to 0.81 and the molar ratio of water / cyanohydrin is equal to 44.27) keeping the temperature of the reaction mixture below 60 ° C. To the heterogeneous reaction medium, 210 g of water are added to obtain a homogeneous mixture. It is kept for 30 minutes at 60 ° C. The analysis of the medium shows that: - 15% of the cyanohydrin has been transformed. the selectivities of HMTBM and AHMTB are, respectively, of 64 and 36%. The mixture is boiled at 104 ° C. After 160 minutes under these conditions, the analysis of the medium shows that: only 29% of the cyanohydrin has been transformed. the selectivities of HMTBM and AHMTB are, respectively, 2 and 98%. The weight ratio of the ammonium sulphate produced with respect to the AHMTB is 0.72. EXAMPLE 1 Test in a closed reactor, at a ratio of H2S? 4 / cyanohydrin = 0.8 (JPZ 262) In a 250 ml glass reactor equipped with: a double jacket whose temperature is regulated by oil circulation, a stirrer, a condenser , - a thermocouple, 60 g of cyanhydrin at 78% by weight are charged. Progressively add 30 g of 95% sulfuric acid (the molar ratio of sulfuric acid / cyanohydrin is equal to 0.8, the molar ratio of water / cyanohydrin is equal to 2.29) keeping the temperature of the reaction mixture below 40 ° C. It is kept for 30 minutes at 35 ° C. The analysis of the medium shows that: all the cyanohydrin has been transformed. - the selectivities of HMTBM and AHMTB are, respectively, 99 and 1%. 40 g of water are added and the reaction mixture is boiled at 110 ° C. After 120 minutes under these conditions, the analysis of the medium shows that: all the cyanohydrin has been transformed. the selectivities of HMTBM and AHMTB are, respectively, 0.3 and 99.7%. The weight ratio of the ammonium sulphate produced with respect to the AHMTB is 0.72.

EXAMPLE 2 Test in a closed reactor, at a ratio of H2S? / Cyanohydrin = 0.7 In a 150 ml glass reactor equipped with: - a double envelope whose temperature is regulated by the circulation of oil, a stirrer, a condenser, a thermocouple, a portion of 75.5 g of cyanohydrin is charged to the 78% by weight in water. 32.2 g of 95% sulfuric acid are progressively added maintaining the temperature of the reaction mixture below 40 ° C (the molar ratio of sulfuric acid / cyanohydrin is equal to 0.69, the molar ratio of water / cyanohydrin is equal to 2.25. ). The temperature is maintained at 40 ° C for 15 minutes. The analysis of the medium shows that all the cyanohydrin has been transformed. The selectivities of HMTBM and AHMTB are, respectively, of 98 and 2%. 55.5 g of water are added and the reaction mixture is boiled at about 107 ° C, to hydrolyze the HMTBM in AHMTB.

After 2 hours in these conditions, the analysis of the medium shows that the selectivities of HMTBM and AHMTB are, respectively, of 2 and 98%. The weight ratio of the ammonium sulphate produced with respect to the AHMTB is 0.61. EXAMPLE 3 Test in closed reactor, at a ratio of H2S? 4 kinahydrin = 0.8 (end of reaction under pressure) In a 250 ml glass reactor equipped with: - a double jacket whose temperature is regulated by the circulation of oil, a agitator, a condenser, a thermocouple, a portion of 102.3 g of cyanohydrin is charged to the 78% by weight in water. 50 g of 95% sulfuric acid are progressively added keeping the temperature of the reaction mixture below 40 ° C (the molar ratio of the sulfuric acid / cyanohydrin is equal to 0.8, the molar ratio of water / cyanohydrin is equal to 2.28. ). The temperature is maintained at 40 ° C for 15 minutes. The analysis of the medium shows that all the cyanohydrin has been transformed. Essentially, HMTBM is obtained. 50.2 g of water are added and the reaction mixture is brought to 90 ° C. After 30 minutes under these conditions the appearance of a precipitate is observed. This precipitate is redissolved by the addition of 10.9 g of water. After 1 hour at 90 ° C, the analysis of the medium shows that the selectivities of HMTBM and AHMTB are, respectively, of 6 and 94%. The reactor is heated to 125 ° C at a pressure of 2.5 bar. An analysis performed after 30 minutes at 125 ° C shows that the selectivities of HMTBM and AHMTB are 0.3 and 99.7%. The weight ratio of the ammonium sulphate produced with respect to the AHMTB is 0.70. EXAMPLE 4 Closed reactor test, at a ratio of H2S? 4 / cyanohydrin = 0.8 (total transformation of HMTBN and HMTBM) In a 5 L glass reactor equipped with: a double jacket whose temperature is regulated by oil circulation, a agitator, a condenser, - a thermocouple, a portion of 768 g of cyanohydrin is charged to the 77% by weight in water. 380 g of 95% sulfuric acid are progressively added keeping the temperature of the reaction mixture below 20 ° C (the molar ratio of the sulfuric acid / cyanohydrin is equal to 0.8, the molar ratio of water / cyanohydrin is equal to 2.41. ). It is heated to 40 ° C and the mixture is kept at this temperature for 20 minutes. The analysis of the medium shows that all the cyanohydrin has been transformed. 501 g of water are added and the mixture is boiled at 110 ° C for 1 hour. The analysis of the medium shows that the selectivities of HMTBM and AHMTB are 0.4 and 99.6%, respectively. The weight ratio of the ammonium sulphate produced with respect to the AHMTB is 0.70. EXAMPLE 5 Test in continuous reactor in vacuum (12 torr), at a ratio of H2SO4 / cinnahydrin = 0.78 A part of a mixture consisting of 163 g / h of 80% cyanohydrin and 62 g / h of water is fed (which corresponds to 225 g / h of HMTBN at 58% by weight) and on the other hand 80 g / h of 95% sulfuric acid. The molar ratio of sulfuric acid / cyanohydrin is equal to 0.78. The temperature of the reactor is maintained at 50 ° C. The pressure is set at 12 torr. Under these conditions it is observed that, in steady state: 65 g / h of water are evaporated, the molar ratio of water / cyanohydrin is equal to 1.88. the transformation of cyanohydrin is 90%. The selectivities of HMTBM and AHMTB are 98 and 2%, respectively. The feed of the reactants is then cut off, the vacuum is cut, the temperature regulation is maintained at 50 ° C and the reaction medium is allowed to evolve. The transformation of the cyanohydrin is followed: 2 minutes after stopping, the transformation of the cyanohydrin is 99%. 13 minutes after stopping, the transformation of the cyanohydrin is 100%. The selectivities of HMTBM and AHMTB are 95 and 5%, respectively. The weight ratio of the ammonium sulfate produced with respect to the AHMTB is 0.69. The 65 g of evaporated water are then added during the first part of the test plus 39 g of supplementary water and the reaction mixture is boiled at 110 ° C for 1 hour. The analysis of the medium shows that the selectivities of HMTBM and AHMTB are 0.4 and 99.6%. EXAMPLE 6 Test in continuous reactor in vacuum (12 torr), at a ratio of H2S? 4 cyanohydrin = 0.6 A part of a mixture consisting of 165 g / h of 80% cyanohydrin and 57 g / h of water is fed, and on the other hand 62 g / h of 95% sulfuric acid. The molar ratio of sulfuric acid / cyanohydrin is equal to 0.6. The temperature of the reactor is maintained at 50 ° C. The pressure is set at 12 torr. Under these conditions it is observed that, in steady state: - 62 g / h of water are evaporated, the molar ratio of water / cyanohydrin is equal to 1.71. the transformation of cyanohydrin is 80%. The selectivities of HMTBM and AHMTB are 98 and 2%, respectively. The feed of the reactants is then cut off, the vacuum is cut, the temperature regulation is maintained at 50 ° C and the reaction medium is allowed to evolve. The transformation of the cyanohydrin is followed: - 5 minutes after stopping, the transformation of the cyanohydrin is 98%. 20 minutes after stopping, the transformation of the cyanohydrin is 99.5%. The selectivities of HMTBM and AHMTB are 95 and 5%, respectively. The weight ratio of the ammonium sulphate produced with respect to the AHMTB is 0.52. Then, as in the previous examples, the water (for example the water evaporated in this stage) can be added and the mixture can be brought to boiling to carry out the hydrolysis of the HMTBM thus formed, to obtain AHMTB. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (14)

1. CLAIMS Having described the invention as an antecedent, the content of the following claims is claimed as property: 1. A process of hydrolysis of 2-hydroxy-4-methylthiobutyronitrile with sulfuric acid, characterized in that a molar amount of sulfuric acid comprised between 0.6 is used. and 0.88 with respect to 2-hydroxy-4-ethylthiobutyronitrile, wherein in a first step the hydration of 2-hydroxy-4-methylthiobutyronitrile in 2-hydroxy-4-methylthiobutyramide is carried out with concentrated sulfuric acid in the presence of a molar ratio of water with respect to 2-hydroxy-4-methylthiobutyronitrile comprised between 1 and 3, and at a temperature less than or equal to 60 ° C, in a second stage proceeds to the hydrolysis of 2-hydroxy-4-methylthiobutyramide to obtain acid 2-hydroxy-4-methylthiobutyric acid, in the presence of an additional quantity of water.
2. 2. A process according to claim 1, characterized in that the molar ratio between sulfuric acid and 2-hydroxy-4-methylthiobutyronitrile is between 0.7 and 0.85.
3. 3. A process according to claim 1, characterized in that the medium leaving the first stage contains less than 5% by weight of 2-hydroxy-4-methylthiobutyric acid and preferably less than 2% by weight. .
4. A process according to claim 1, characterized in that the medium leaving the first stage contains more than 95% by weight of 2-hydroxy-4-methylthiobutyramide and preferably more than 98% by weight,.
5. 5. A process according to claim 1, characterized in that during the first stage the molar amount of water with respect to 2-hydroxy-4-methylthiobutyronitrile is comprised between 1 and 2.5 moles.
6. 6. A method according to claim 1, characterized in that the first step is carried out at a temperature comprised between 0 and 50 ° C.
7. 7. A method according to claim 1, characterized in that the first stage is carried out at a pressure comprised between 0.01 and 3 bars.
8. 8. A process according to claim 1, characterized in that during the second stage a sufficient amount of water is added to maintain the reaction medium in a homogeneous form.
9. 9. A process according to claim 8, characterized in that the minimum amount of water during the second stage is 28% by weight with respect to the reaction medium.
10. 10. A method according to claim 1, characterized in that the second step is carried out at a temperature comprised between 90 and 130 ° C.
11. 11. A method according to claim 1, characterized in that the second stage is carried out at a pressure comprised between 0.5 and 5 bars.
12. 12. A process according to any of claims 1 or 5, characterized in that a concentrated solution of 2-hydroxy-4-methylthiobutyronitrile is used in the first step.
13. 13. A process according to any of claims 1 or 5, characterized in that in the first stage an aqueous solution of 2-hydroxy-4-methylthiobutyronitrile is used, which is concentrated in the course of the first stage by evaporation of Water.
14. 14. A method according to claim 13, characterized in that the evaporated water is recycled to the second stage.